Several Helicobacter species are the cause of pathogenesis of the gastric epithelium. Helicobacter pylori, and to a lesser extent H. heilmannii are known to cause gastritis, a major factor in the development of peptic ulcers and gastric lymphoma in humans. Helicobacter felis is most likely the cause of gastric infections in both cats and dogs. In order to survive the highly acidic environment of the stomach, members of the Helicobacter family produce a urease that is capable of hydrolysing the urea present in gastric juice. This hydrolysation sets free an amount of NH4OH that suffices to neutralise the environment of the bacterium. It is known that the urease plays a role in the colonization of the bacterium as well as in its pathogenesis.
Genes encoding urease have been described and sequenced for both Helicobacter pylori (Labigne et al., J. Bacteriol. 173: 1920-1931 (1991)) and Helicobacter felis (Ferrero et al., Molec. Microbiol. 9, 323-333 (1993)). Of the seven genes involved in urease expression and secretion, only two genes encode the two structural subunits urease A and B of the urease enzyme, ureA and ureB. These two polypeptides form a polypeptide complex having urease activity.
Vaccines against infections caused by both H. pylori and felis have been made and have been the subject of i.a. International Patent Applications WO 94/09823 and WO 96/34624. Several attempt have been made to use H. pylori urease as a vaccine component for the protection of cats against H. felis infection. Although indeed a certain level of protection can be obtained, the results are far from the 100% protection that would be desirable. From animal experiments published so far, it becomes clear that a significant number of animals vaccinated with H. pylori is not at all protected against subsequent challenge with H. felis. Protection of cats vaccinated with purified urease from either H. felis or pylori has not been described. Vaccinating cats with H. felis whole cell lysates might theoretically be feasible but is not a practical option. This is because in spite of many attempts for improvement, H. felis is difficult to grow.
There clearly is a need for an efficacious vaccine, based upon homologous components, and it is clear that the known H. felis urease does not confer full protection.